Methylation
Methylation, in the chemical sciences, is the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These terms are commonly used in chemistry, biochemistry, soil science, and biology.
In
In biology
In biological systems, methylation is accomplished by enzymes. Methylation can modify heavy metals and can regulate gene expression, RNA processing, and protein function. It is a key process underlying epigenetics.
Methanogenesis
Methanogenesis, the process that generates methane from CO2, involves a series of methylation reactions. These reactions are caused by a set of enzymes harbored by a family of anaerobic microbes.[1]
In reverse methanogenesis, methane is the methylating agent.[citation needed]
O-methyltransferases
A wide variety of phenols undergo O-methylation to give anisole derivatives. This process, catalyzed by such enzymes as caffeoyl-CoA O-methyltransferase, is a key reaction in the biosynthesis of lignols, percursors to lignin, a major structural component of plants.
Plants produce flavonoids and isoflavones with methylations on hydroxyl groups, i.e.
Proteins
Along with ubiquitination and phosphorylation, methylation is a major biochemical process for modifying protein function. The most prevalent protein methylations affect arginine and lysine residue of specific histones. Otherwise histidine, glutamate, asparagine, cysteine are susceptible to methylation. Some of these products include S-methylcysteine, two isomers of N-methylhistidine, and two isomers of N-methylarginine.[2]
Methionine synthase
In methylcobalamin-dependent forms of the enzyme, the reaction proceeds by two steps in a ping-pong reaction. The enzyme is initially primed into a reactive state by the transfer of a methyl group from N5-MeTHF to Co(I) in enzyme-bound
Heavy metals: arsenic, mercury, cadmium
Biomethylation is the pathway for converting some heavy elements into more mobile or more lethal derivatives that can enter the
Epigenetic methylation
DNA/RNA methylation
In honey bees, DNA methylation is associated with alternative splicing and gene regulation based on functional genomic research published in 2013.[12] In addition, DNA methylation is associated with expression changes in immune genes when honey bees were under lethal viral infection.[13] Several review papers have been published on the topics of DNA methylation in social insects.[14][15]
RNA methylation occurs in different RNA species viz.
N6-methyladenosine (m6A) is the most common and abundant methylation modification in RNA molecules (mRNA) present in eukaryotes. 5-methylcytosine (5-mC) also commonly occurs in various RNA molecules. Recent data strongly suggest that m6A and 5-mC RNA methylation affects the regulation of various biological processes such as RNA stability and mRNA translation,[17] and that abnormal RNA methylation contributes to etiology of human diseases.[18]
In social insects such as honey bees, RNA methylation is studied as a possible epigenetic mechanism underlying aggression via reciprocal crosses.[19]
Protein methylation
Evolution
Methyl metabolism is very ancient and can be found in all organisms on earth, from bacteria to humans, indicating the importance of methyl metabolism for physiology.[23] Indeed, pharmacological inhibition of global methylation in species ranging from human, mouse, fish, fly, roundworm, plant, algae, and cyanobacteria causes the same effects on their biological rhythms, demonstrating conserved physiological roles of methylation during evolution.[24]
In chemistry
The term methylation in organic chemistry refers to the alkylation process used to describe the delivery of a CH3 group.[25]
Electrophilic methylation
Methylations are commonly performed using
The
Eschweiler–Clarke methylation
The
Diazomethane and trimethylsilyldiazomethane
Diazomethane and the safer analogue trimethylsilyldiazomethane methylate carboxylic acids, phenols, and even alcohols:
The method offers the advantage that the side products are easily removed from the product mixture.[35]
Nucleophilic methylation
Methylation sometimes involve use of
Milder methylating agents include tetramethyltin, dimethylzinc, and trimethylaluminium.[38]
See also
Biology topics
- Bisulfite sequencing – the biochemical method used to determine the presence or absence of methyl groups on a DNA sequence
- MethDB DNA Methylation Database
- Microscale thermophoresis – a biophysical method to determine the methylisation state of DNA[39]
Organic chemistry topics
- Alkylation
- Methoxy
- Titanium–zinc methylenation
- Petasis reagent
- Nysted reagent
- Wittig reaction
- Tebbe's reagent
References
- ^ Thauer, R. K., "Biochemistry of Methanogenesis: a Tribute to Marjory Stephenson", Microbiology, 1998, volume 144, pages 2377-2406.
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- ^ Stewart, Kendal (15 September 2017). "Methylation (MTHFR) Testing & Folate Deficiency". Archived from the original on 12 October 2017. Retrieved 11 October 2017.
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- ISBN 978-0-9747077-3-0.
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External links
- deltaMasses Detection of Methylations after Mass Spectrometry